4-Ethoxymethylphenol: A novel phytoestrogen that acts as an agonist for human estrogen receptors

Virginia Pearce, Zafar Nawaz, Wu Xiao, David Wiedenfeld, Nick Boyle, Don Smith

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Estrogen is the natural agonist of the estrogen receptor (ER). However, certain plant-derived compounds or phytoestrogens have been identified that mimic estrogens and act as agonists and/or antagonists of ERs, depending on subtype and target tissue. Using thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), and proton nuclear magnetic resonance (1H-NMR), we identified a simple phenol, 4-ethoxymethylphenol (4EM), found in Maclura pomifera that acts as an agonist of ER-α and ER-β in HeLa and MCF-7 cells. To study the effect of 4EM on ER-α and ER-β activity, we performed transient transfection assays and showed that 4EM activated ER-dependent gene transcription in a dose-dependent manner on both ER subtypes and this activity was inhibited by trans-4-hydroxytamoxifen (4HT). Further, 4EM-mediated transcription in ER-α, like estrogen, was enhanced in the presence of coactivators, steroid receptor coactivator-1 (SRC-1), CREB binding proteins (CBP), and E6-associated protein (E6-AP). We found that 4EM was specific for ER and did not activate transcription of the progesterone receptor.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number4
StatePublished - Mar 2003
Externally publishedYes


  • 4-Ethoxymethylphenol
  • 4HT
  • Agonist
  • CBP
  • Coactivators
  • E6-AP
  • ER-α
  • ER-β
  • Estrogen
  • Estrogen receptor
  • Maclura pomifera
  • Phytoestrogens
  • Progesterone receptor
  • SRC-1
  • Tamoxifen

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology


Dive into the research topics of '4-Ethoxymethylphenol: A novel phytoestrogen that acts as an agonist for human estrogen receptors'. Together they form a unique fingerprint.

Cite this